Effect of laparoscopic-assisted resection vs open resection of stage II or III rectal cancer on pathologic outcomes the ACOSOG Z6051 randomized clinical trial

James Fleshman, Megan Branda, Daniel J. Sargent, Anne Marie Boller, Virgilio George, Maher Abbas, Walter R. Peters, Dipen Maun, George Chang, Alan Joseph Herline, Alessandro Fichera, Matthew Mutch, Steven Wexner, Mark Whiteford, John Marks, Elisa Birnbaum, David Margolin, David Larson, Peter Marcello, Mitchell Posner & 5 others Thomas Read, John Monson, Sherry M. Wren, Peter W.T. Pisters, Heidi Nelson

Research output: Contribution to journalArticle

345 Citations (Scopus)

Abstract

IMPORTANCE: Evidence about the efficacy of laparoscopic resection of rectal cancer is incomplete, particularly for patients with more advanced-stage disease. OBJECTIVE: To determine whether laparoscopic resection is noninferior to open resection, as determined by gross pathologic and histologic evaluation of the resected proctectomy specimen. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, balanced, noninferiority, randomized trial enrolled patients between October 2008 and September 2013. The trial was conducted by credentialed surgeons from 35 institutions in the United States and Canada. A total of 486 patients with clinical stage II or III rectal cancer within 12 cm of the anal verge were randomized after completion of neoadjuvant therapy to laparoscopic or open resection. INTERVENTIONS: Standard laparoscopic and open approaches were performed by the credentialed surgeons. MAIN OUTCOMES AND MEASURES: The primary outcome assessing efficacywas a composite of circumferential radial margin greater than 1 mm, distal margin without tumor, and completeness of total mesorectal excision. A 6% noninferiority margin was chosen according to clinical relevance estimation. RESULTS: Two hundred forty patients with laparoscopic resection and 222 with open resection were evaluable for analysis of the 486 enrolled. Successful resection occurred in 81.7%of laparoscopic resection cases (95%CI, 76.8%-86.6%) and 86.9%of open resection cases (95%CI, 82.5%-91.4%) and did not support noninferiority (difference, -5.3%; 1-sided 95%CI, -10.8%to ∞; P for noninferiority = .41). Patients underwent low anterior resection (76.7%) or abdominoperineal resection (23.3%). Conversion to open resection occurred in 11.3%of patients. Operative time was significantly longer for laparoscopic resection (mean, 266.2 vs 220.6 minutes; mean difference, 45.5 minutes; 95%CI, 27.7-63.4; P < .001). Length of stay (7.3 vs 7.0 days; mean difference, 0.3 days; 95%CI, -0.6 to 1.1), readmission within 30 days (3.3%vs 4.1%; difference, -0.7%; 95%CI, -4.2% to 2.7%), and severe complications (22.5%vs 22.1%; difference, 0.4%; 95%CI, ?4.2%to 2.7%) did not differ significantly. Quality of the total mesorectal excision specimen in 462 operated and analyzed surgeries was complete (77%) and nearly complete (16.5%) in 93.5%of the cases. Negative circumferential radial margin was observed in 90% of the overall group (87.9% laparoscopic resection and 92.3%open resection; P = .11). Distal margin result was negative in more than 98%of patients irrespective of type of surgery (P = .91). CONCLUSIONS AND RELEVANCE: Among patients with stage II or III rectal cancer, the use of laparoscopic resection compared with open resection failed to meet the criterion for noninferiority for pathologic outcomes. Pending clinical oncologic outcomes, the findings do not support the use of laparoscopic resection in these patients.

Original languageEnglish (US)
Pages (from-to)1346-1355
Number of pages10
JournalJAMA - Journal of the American Medical Association
Volume314
Issue number13
DOIs
StatePublished - Oct 6 2015

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Rectal Neoplasms
Randomized Controlled Trials
Neoadjuvant Therapy
Operative Time
Canada
Length of Stay

ASJC Scopus subject areas

  • Medicine(all)

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Effect of laparoscopic-assisted resection vs open resection of stage II or III rectal cancer on pathologic outcomes the ACOSOG Z6051 randomized clinical trial. / Fleshman, James; Branda, Megan; Sargent, Daniel J.; Boller, Anne Marie; George, Virgilio; Abbas, Maher; Peters, Walter R.; Maun, Dipen; Chang, George; Herline, Alan Joseph; Fichera, Alessandro; Mutch, Matthew; Wexner, Steven; Whiteford, Mark; Marks, John; Birnbaum, Elisa; Margolin, David; Larson, David; Marcello, Peter; Posner, Mitchell; Read, Thomas; Monson, John; Wren, Sherry M.; Pisters, Peter W.T.; Nelson, Heidi.

In: JAMA - Journal of the American Medical Association, Vol. 314, No. 13, 06.10.2015, p. 1346-1355.

Research output: Contribution to journalArticle

Fleshman, J, Branda, M, Sargent, DJ, Boller, AM, George, V, Abbas, M, Peters, WR, Maun, D, Chang, G, Herline, AJ, Fichera, A, Mutch, M, Wexner, S, Whiteford, M, Marks, J, Birnbaum, E, Margolin, D, Larson, D, Marcello, P, Posner, M, Read, T, Monson, J, Wren, SM, Pisters, PWT & Nelson, H 2015, 'Effect of laparoscopic-assisted resection vs open resection of stage II or III rectal cancer on pathologic outcomes the ACOSOG Z6051 randomized clinical trial', JAMA - Journal of the American Medical Association, vol. 314, no. 13, pp. 1346-1355. https://doi.org/10.1001/jama.2015.10529
Fleshman, James ; Branda, Megan ; Sargent, Daniel J. ; Boller, Anne Marie ; George, Virgilio ; Abbas, Maher ; Peters, Walter R. ; Maun, Dipen ; Chang, George ; Herline, Alan Joseph ; Fichera, Alessandro ; Mutch, Matthew ; Wexner, Steven ; Whiteford, Mark ; Marks, John ; Birnbaum, Elisa ; Margolin, David ; Larson, David ; Marcello, Peter ; Posner, Mitchell ; Read, Thomas ; Monson, John ; Wren, Sherry M. ; Pisters, Peter W.T. ; Nelson, Heidi. / Effect of laparoscopic-assisted resection vs open resection of stage II or III rectal cancer on pathologic outcomes the ACOSOG Z6051 randomized clinical trial. In: JAMA - Journal of the American Medical Association. 2015 ; Vol. 314, No. 13. pp. 1346-1355.
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title = "Effect of laparoscopic-assisted resection vs open resection of stage II or III rectal cancer on pathologic outcomes the ACOSOG Z6051 randomized clinical trial",
abstract = "IMPORTANCE: Evidence about the efficacy of laparoscopic resection of rectal cancer is incomplete, particularly for patients with more advanced-stage disease. OBJECTIVE: To determine whether laparoscopic resection is noninferior to open resection, as determined by gross pathologic and histologic evaluation of the resected proctectomy specimen. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, balanced, noninferiority, randomized trial enrolled patients between October 2008 and September 2013. The trial was conducted by credentialed surgeons from 35 institutions in the United States and Canada. A total of 486 patients with clinical stage II or III rectal cancer within 12 cm of the anal verge were randomized after completion of neoadjuvant therapy to laparoscopic or open resection. INTERVENTIONS: Standard laparoscopic and open approaches were performed by the credentialed surgeons. MAIN OUTCOMES AND MEASURES: The primary outcome assessing efficacywas a composite of circumferential radial margin greater than 1 mm, distal margin without tumor, and completeness of total mesorectal excision. A 6{\%} noninferiority margin was chosen according to clinical relevance estimation. RESULTS: Two hundred forty patients with laparoscopic resection and 222 with open resection were evaluable for analysis of the 486 enrolled. Successful resection occurred in 81.7{\%}of laparoscopic resection cases (95{\%}CI, 76.8{\%}-86.6{\%}) and 86.9{\%}of open resection cases (95{\%}CI, 82.5{\%}-91.4{\%}) and did not support noninferiority (difference, -5.3{\%}; 1-sided 95{\%}CI, -10.8{\%}to ∞; P for noninferiority = .41). Patients underwent low anterior resection (76.7{\%}) or abdominoperineal resection (23.3{\%}). Conversion to open resection occurred in 11.3{\%}of patients. Operative time was significantly longer for laparoscopic resection (mean, 266.2 vs 220.6 minutes; mean difference, 45.5 minutes; 95{\%}CI, 27.7-63.4; P < .001). Length of stay (7.3 vs 7.0 days; mean difference, 0.3 days; 95{\%}CI, -0.6 to 1.1), readmission within 30 days (3.3{\%}vs 4.1{\%}; difference, -0.7{\%}; 95{\%}CI, -4.2{\%} to 2.7{\%}), and severe complications (22.5{\%}vs 22.1{\%}; difference, 0.4{\%}; 95{\%}CI, ?4.2{\%}to 2.7{\%}) did not differ significantly. Quality of the total mesorectal excision specimen in 462 operated and analyzed surgeries was complete (77{\%}) and nearly complete (16.5{\%}) in 93.5{\%}of the cases. Negative circumferential radial margin was observed in 90{\%} of the overall group (87.9{\%} laparoscopic resection and 92.3{\%}open resection; P = .11). Distal margin result was negative in more than 98{\%}of patients irrespective of type of surgery (P = .91). CONCLUSIONS AND RELEVANCE: Among patients with stage II or III rectal cancer, the use of laparoscopic resection compared with open resection failed to meet the criterion for noninferiority for pathologic outcomes. Pending clinical oncologic outcomes, the findings do not support the use of laparoscopic resection in these patients.",
author = "James Fleshman and Megan Branda and Sargent, {Daniel J.} and Boller, {Anne Marie} and Virgilio George and Maher Abbas and Peters, {Walter R.} and Dipen Maun and George Chang and Herline, {Alan Joseph} and Alessandro Fichera and Matthew Mutch and Steven Wexner and Mark Whiteford and John Marks and Elisa Birnbaum and David Margolin and David Larson and Peter Marcello and Mitchell Posner and Thomas Read and John Monson and Wren, {Sherry M.} and Pisters, {Peter W.T.} and Heidi Nelson",
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TY - JOUR

T1 - Effect of laparoscopic-assisted resection vs open resection of stage II or III rectal cancer on pathologic outcomes the ACOSOG Z6051 randomized clinical trial

AU - Fleshman, James

AU - Branda, Megan

AU - Sargent, Daniel J.

AU - Boller, Anne Marie

AU - George, Virgilio

AU - Abbas, Maher

AU - Peters, Walter R.

AU - Maun, Dipen

AU - Chang, George

AU - Herline, Alan Joseph

AU - Fichera, Alessandro

AU - Mutch, Matthew

AU - Wexner, Steven

AU - Whiteford, Mark

AU - Marks, John

AU - Birnbaum, Elisa

AU - Margolin, David

AU - Larson, David

AU - Marcello, Peter

AU - Posner, Mitchell

AU - Read, Thomas

AU - Monson, John

AU - Wren, Sherry M.

AU - Pisters, Peter W.T.

AU - Nelson, Heidi

PY - 2015/10/6

Y1 - 2015/10/6

N2 - IMPORTANCE: Evidence about the efficacy of laparoscopic resection of rectal cancer is incomplete, particularly for patients with more advanced-stage disease. OBJECTIVE: To determine whether laparoscopic resection is noninferior to open resection, as determined by gross pathologic and histologic evaluation of the resected proctectomy specimen. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, balanced, noninferiority, randomized trial enrolled patients between October 2008 and September 2013. The trial was conducted by credentialed surgeons from 35 institutions in the United States and Canada. A total of 486 patients with clinical stage II or III rectal cancer within 12 cm of the anal verge were randomized after completion of neoadjuvant therapy to laparoscopic or open resection. INTERVENTIONS: Standard laparoscopic and open approaches were performed by the credentialed surgeons. MAIN OUTCOMES AND MEASURES: The primary outcome assessing efficacywas a composite of circumferential radial margin greater than 1 mm, distal margin without tumor, and completeness of total mesorectal excision. A 6% noninferiority margin was chosen according to clinical relevance estimation. RESULTS: Two hundred forty patients with laparoscopic resection and 222 with open resection were evaluable for analysis of the 486 enrolled. Successful resection occurred in 81.7%of laparoscopic resection cases (95%CI, 76.8%-86.6%) and 86.9%of open resection cases (95%CI, 82.5%-91.4%) and did not support noninferiority (difference, -5.3%; 1-sided 95%CI, -10.8%to ∞; P for noninferiority = .41). Patients underwent low anterior resection (76.7%) or abdominoperineal resection (23.3%). Conversion to open resection occurred in 11.3%of patients. Operative time was significantly longer for laparoscopic resection (mean, 266.2 vs 220.6 minutes; mean difference, 45.5 minutes; 95%CI, 27.7-63.4; P < .001). Length of stay (7.3 vs 7.0 days; mean difference, 0.3 days; 95%CI, -0.6 to 1.1), readmission within 30 days (3.3%vs 4.1%; difference, -0.7%; 95%CI, -4.2% to 2.7%), and severe complications (22.5%vs 22.1%; difference, 0.4%; 95%CI, ?4.2%to 2.7%) did not differ significantly. Quality of the total mesorectal excision specimen in 462 operated and analyzed surgeries was complete (77%) and nearly complete (16.5%) in 93.5%of the cases. Negative circumferential radial margin was observed in 90% of the overall group (87.9% laparoscopic resection and 92.3%open resection; P = .11). Distal margin result was negative in more than 98%of patients irrespective of type of surgery (P = .91). CONCLUSIONS AND RELEVANCE: Among patients with stage II or III rectal cancer, the use of laparoscopic resection compared with open resection failed to meet the criterion for noninferiority for pathologic outcomes. Pending clinical oncologic outcomes, the findings do not support the use of laparoscopic resection in these patients.

AB - IMPORTANCE: Evidence about the efficacy of laparoscopic resection of rectal cancer is incomplete, particularly for patients with more advanced-stage disease. OBJECTIVE: To determine whether laparoscopic resection is noninferior to open resection, as determined by gross pathologic and histologic evaluation of the resected proctectomy specimen. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, balanced, noninferiority, randomized trial enrolled patients between October 2008 and September 2013. The trial was conducted by credentialed surgeons from 35 institutions in the United States and Canada. A total of 486 patients with clinical stage II or III rectal cancer within 12 cm of the anal verge were randomized after completion of neoadjuvant therapy to laparoscopic or open resection. INTERVENTIONS: Standard laparoscopic and open approaches were performed by the credentialed surgeons. MAIN OUTCOMES AND MEASURES: The primary outcome assessing efficacywas a composite of circumferential radial margin greater than 1 mm, distal margin without tumor, and completeness of total mesorectal excision. A 6% noninferiority margin was chosen according to clinical relevance estimation. RESULTS: Two hundred forty patients with laparoscopic resection and 222 with open resection were evaluable for analysis of the 486 enrolled. Successful resection occurred in 81.7%of laparoscopic resection cases (95%CI, 76.8%-86.6%) and 86.9%of open resection cases (95%CI, 82.5%-91.4%) and did not support noninferiority (difference, -5.3%; 1-sided 95%CI, -10.8%to ∞; P for noninferiority = .41). Patients underwent low anterior resection (76.7%) or abdominoperineal resection (23.3%). Conversion to open resection occurred in 11.3%of patients. Operative time was significantly longer for laparoscopic resection (mean, 266.2 vs 220.6 minutes; mean difference, 45.5 minutes; 95%CI, 27.7-63.4; P < .001). Length of stay (7.3 vs 7.0 days; mean difference, 0.3 days; 95%CI, -0.6 to 1.1), readmission within 30 days (3.3%vs 4.1%; difference, -0.7%; 95%CI, -4.2% to 2.7%), and severe complications (22.5%vs 22.1%; difference, 0.4%; 95%CI, ?4.2%to 2.7%) did not differ significantly. Quality of the total mesorectal excision specimen in 462 operated and analyzed surgeries was complete (77%) and nearly complete (16.5%) in 93.5%of the cases. Negative circumferential radial margin was observed in 90% of the overall group (87.9% laparoscopic resection and 92.3%open resection; P = .11). Distal margin result was negative in more than 98%of patients irrespective of type of surgery (P = .91). CONCLUSIONS AND RELEVANCE: Among patients with stage II or III rectal cancer, the use of laparoscopic resection compared with open resection failed to meet the criterion for noninferiority for pathologic outcomes. Pending clinical oncologic outcomes, the findings do not support the use of laparoscopic resection in these patients.

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